This is a continuing investigation of the pathogenesis of senile dementia of the Alzheimer type (SDAT), and of pre-senile Alzeheimer's Disease (AD). We have shown by cell counts that there is no major decrement of cortical neurons relative to age-matched controls, and biochemically that there is maintenance of the cortical muscarinic receptor of acetylcholine, whether there is a 75 - 90% loss of cortical choline acetyltransferase (ChAT) in these patients. We now propose to localize the synthetic enzyme, ChAT, and the receptor in human and animal brain tissue by enzyme and immunohistochemistry and by radioautography. Both light and electron microscopy will be used to compare young brains with normal old, and SDAT brains with normal old. We expect to determine whether there is a specific defect in still viable cells. We will determine the relationships among histologic lesions (plaques and tangles), acetylcholine receptor and ChAt activity. We will also study in vivo and in vitro the morphologic effects on nervous tissue of blocking the synthesis of acetylcholine with antibody to ChAT and with hemicholinium-3, which specifically blocks the neuronal high affinity uptake system for choline.